1,721,037 research outputs found
Structural Specificity of the Biological Activity of Human and Murine Stem Cell Factor in Stress Erythropoiesis
No full textThe Genetic Makeup of Myeloproliferative Neoplasms: Role of Germline Variants in Defining Disease Risk, Phenotypic Diversity and Outcome
Full text linkMyeloproliferative neoplasms are hematologic malignancies typified by a substantial heritable component. Germline variants may affect the risk of developing a MPN, as documented by GWAS studies on large patient cohorts. In addition, once the MPN occurred, inherited host genetic factors can be responsible for tuning the disease phenotypic presentation, outcome, and response to therapy. This review covered the polymorphisms that have been variably associated to MPNs, discussing them in the functional perspective of the biological pathways involved. Finally, we reviewed host genetic determinants of clonal hematopoiesis, a pre-malignant state that may anticipate overt hematologic neoplasms including MPNs
The A3669G Polymorphism of GR Is a Host Genetic Modifier Associated with Polycythemia Vera and Primary Myelofibrosis
No full textNovel role of PKC epsilon in mitotic spindle stability.
Full text linkMitosis is a highly regulated process characterized by dramatic and coordinated
morphological changes to ensure the fidelity of chromosome segregation. Missegregation
of mitotic chromosomes leads to a condition that underlies chromosomal
instability(1), which is a hallmark of cancer. In order to assure symmetry and bipolarity
of the cell division process, mitotic spindle microtubules properly segregate
mitotic chromosomes (2). Among the several isoforms of serine/threonine kinases,
PKCε is one of the best understood for its role as a transforming oncogene, and it
has been found overexpressed in different types of tumors. In 2008, Saurin and colleagues
demonstrated the involvement of PKCε in the regulation of the late stage of
mitosis (3). Through its association with 14-3-3 at the midbody, PKCε is essential for
the successful completion of cytokinesis, and the inhibition of functional PKCε-14-3-
3 complex leads to abscission failure and multinucleated phenotype in cells. In this
study, we found that PKCε is involved in mitotic spindle stability. Using fluorescence
microscopy, we found that the active form of PKCε (phosphorylated at Ser-729), colocalizes
to the centrosome in cells in metaphase, where the mitotic spindle nucleation
occurs. Furthermore, experiments of co-immunoprecipitation revealed that, when
cells are synchronized in metaphase, PKCɛ is associated to ɣ-tubulin, a member of
the tubulin superfamily localized to the microtubule organizing centers and is essential
for microtubule nucleation from centrosomes. Consequently modulation of PKCɛ
expression affects spindle stability: PKCɛ downregulation by specific shRNA results
in mitotic spindle disorganization with a reduction of the amount of centrosomal and
mitotic ɣ-Tubulin and αβ-tubulin fluorescence. Mitotic spindle formation assays using
Nocodazole, known to interfere with the polymerization of microtubules, revealed
that cells lacking PKCɛ were unable to regrow microtubules after depolymerization.
These results reveal a novel role of PKCɛ in mitotic spindle stability, which likely
determinant for genome stability
Evolution led humans to bipedalism, but we live in a sedentary society: Will "Sunday running" protect us from NCDs at no cost?
Full text link: Evolution led humans to bipedal stance and movement. However, we live in a sedentary society that strongly challenges our willingness to be physically active. We (mis)understand that being at least a Sunday runner could protect us from sedentary-related diseases, but what if this compromises the healthier life expectancy anyway? Citing Paul Gauguin, we know where we come from and what we are, the question arises about where we are going. And also, how
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